A homeobox (HB) encodes a protein domain, the homeodomain (HD), which is a conserved 60-amino acid motif present in transcription factors found in all the eukaryotic organisms. This 60-amino acid sequence folds into a characteristic three-helix structure that is able to interact specifically with DNA. Most HDs are able to bind DNA as monomers with high affinity, through interactions made by helix III (the so-called recognition helix) and a disordered N-terminal arm located beyond helix I. The high degree of conservation of this type of domain among diverse proteins from different kingdoms indicates that this structure is crucial to maintain the HD functionality and that the role played by this domain is vital.